Department of Pharmacology and Systems Physiology, University of Cincinnati-College of Medicine, Cincinnati, Ohio, USA.
Neuroendocrinology. 2022;112(3):287-297. doi: 10.1159/000516834. Epub 2021 Apr 27.
The control of energy balance relies on the counterbalancing release of neuropeptides encoded by the pro-opiomelanocortin (Pomc) and agouti-related protein (Agrp) genes, expressed by 2 distinct neuronal populations of the arcuate (ARC) nucleus of the hypothalamus. Although largely segregated, single-cell resolution techniques demonstrate some degree of co-expression. We studied whether challenges to the control of energy balance influence the degree of Agrp and Pomc co-expression in ARC melanocortin neurons.
We used fluorescence-activated cell sorting followed by quantitative polymerase chain reaction and fluorescent in situ hybridization to measure Pomc and Agrp gene co-expression in POMC or AGRP neurons in response to (1) acute or chronic calorie restriction, or (2) obesity due to loss of leptin receptor expression or chronic high-fat diet feeding in male mice.
Melanocortin ARC neurons of fed mice exhibited low, yet detectable, levels of Pomc and Agrp gene co-expression. Calorie restriction significantly increased and decreased total Agrp and Pomc expression, respectively, and reduced the expression of Pomc relative to Agrp in AGRP neurons. Leptin-deficient db/db mice showed increased total Agrp levels and decreased Pomc expression, as well as significantly increased Agrp expression relative to Pomc in POMC neurons. Expression or co-expression levels did not differ between diet-induced obese mice and lean controls.
Changes in Agrp and Pomc co-expression within POMC and AGRP neurons following chronic calorie restriction or in db/db mice suggest an additional mechanism to further suppress the melanocortin signaling during conditions of severely reduced leptin action.
能量平衡的控制依赖于由 pro-opiomelanocortin（Pomc）和 agouti 相关蛋白（Agrp）基因编码的神经肽的平衡释放，这些基因由下丘脑弓状核（ARC）的 2 个不同神经元群体表达。尽管它们在很大程度上是分开的，但单细胞分辨率技术表明存在一定程度的共表达。我们研究了能量平衡控制的挑战是否会影响 ARC 黑色素皮质素神经元中 Agrp 和 Pomc 共表达的程度。
我们使用荧光激活细胞分选，然后进行定量聚合酶链反应和荧光原位杂交，以测量 Pomc 和 Agrp 基因在 POMC 或 AGRP 神经元中的共表达，以响应（1）急性或慢性热量限制，或（2）由于瘦素受体表达缺失或慢性高脂肪饮食喂养导致的肥胖在雄性小鼠中。
进食小鼠的黑色素皮质素 ARC 神经元表现出低水平但可检测到的 Pomc 和 Agrp 基因共表达。热量限制分别显著增加和减少了 Agrp 和 Pomc 的总表达，并降低了 AGRP 神经元中 Pomc 相对于 Agrp 的表达。瘦素缺乏型 db/db 小鼠表现出 Agrp 总水平升高和 Pomc 表达降低，以及 POMC 神经元中 Agrp 相对于 Pomc 的表达显著增加。饮食诱导肥胖的小鼠和瘦对照之间的表达或共表达水平没有差异。
慢性热量限制或 db/db 小鼠中 POMC 和 AGRP 神经元中 Agrp 和 Pomc 共表达的变化表明，在瘦素作用严重降低的情况下，进一步抑制黑色素皮质素信号的另一种机制。
